Media release

From: Murdoch Children's Research Institute (MCRI)

Research at a Glance:

• An international study has found rapid genome sequencing, that can detect rare genetic diseases within weeks, is highly effective at diagnosing the cause of epilepsy in babies and leads to better treatment options in most cases
• Rapid genome sequencing had a high diagnostic rate of 43 per cent for infantile epilepsy. More than half of the babies who received a diagnosis had their treatment plan changed
• The researchers stated the results demonstrated the feasibility and benefits of performing early rapid genome sequencing in the health-care systems of four countries, highlighting the need for greater access to the technology in clinical care

Rapid genome sequencing, that can detect rare genetic diseases within weeks, is highly effective at diagnosing babies with epilepsy and leads to better treatment options in most cases, according to a global study.

The research, published in The Lancet Neurology, found rapid genome sequencing had a high diagnostic rate of 43 per cent for infantile epilepsy, supporting the need for greater access to the cutting-edge technology in clinical care.

Infantile epilepsy is a neurological disorder, which causes recurrent and unprovoked seizures, and often leads to serious, lifelong developmental and cognitive delays. Most forms of infantile epilepsy have a genetic cause.

The international study, the first to examine rapid genome sequencing in children with a specific health condition, recruited 100 babies with new-onset epilepsy from Australia, Canada, the UK and the US.

Part of the International Precision Child Health Partnership (IPCHiP), an international consortium, which aims to use genomic data to accelerate discovery and therapeutic development, the Gene-STEPS study was co-led by Murdoch Children's Research Institute, The Hospital for Sick Children (SickKids), Boston Children's Hospital, UCL Great Ormond Street Institute for Child Health and Great Ormond Street Hospital. IPCHiP is the first major global clinical collaboration around genomics and precision child health.

Murdoch Children’s Dr Katherine Howell said early recognition and prompt treatment of infantile epilepsy were crucial to improving health outcomes and preventing further neurological deterioration. The study found 56 per cent of babies who received a diagnosis had their treatment plan changed as result.

“Uncontrolled seizures in a baby’s developing brain can lead to high rates of developmental setbacks,” Dr Howell said. Identifying the cause early can help guide treatment options, such as medication changes, which can improve seizure control. However, current genetic testing methods often take months or even years, resulting in missed opportunities.”

Unlike more targeted genetic testing that is often used to confirm a suspected diagnosis, rapid genome sequencing looks for any changes in a person’s DNA that may explain a medical condition. The technology involves analysing the entire genome, the complete set of an organism's genetic material. Currently, there are more than 800 different genetic causes of infantile epilepsy and many have similar symptoms during infancy.

“We expect rapid genome sequencing to improve the outcomes of babies with epilepsy by providing individualised care, tailored to the underlying cause, at the earliest possible stage,” Dr Howell said. More than half who received a diagnosis in our study saw their treatment change, a remarkable outcome for this vulnerable population.”

But for those whose results did not provide a genetic explanation for their seizures, SickKids Dr Vann Chau said a negative test was also an important piece of information for families.

“Regardless of whether sequencing shows there is a genetic cause, the information gathered from genome sequencing helps clinicians develop a care plan that is specific to the medical needs of each patient,” he said.

Melbourne mum Karsha Trowbridge's son Levi, 3, has KCNQ2 epileptic encephalopathy, a rare genetic disorder that triggers frequent seizures. He was diagnosed as a newborn via rapid genomic testing.

"I had just bought Levi home from the hospital when he had his first major seizure," she said. It was a terrifying time in the weeks that followed, watching your baby having multiple seizures a day, and at times, turning blue and holding his breath. But when we got a diagnosis that changed everything. We were no longer kept in the dark, not knowing how to help our child.”

Karsha said after changing medications due to the diagnosis, Levi went from having five seizures a day to only a handful a year.

“If we had been waiting years for a diagnosis, his development and learning may never have progressed,” she said. It’s likely he wouldn’t have walked, talked and breathed on his own. Early intervention is crucial because every seizure, no matter how small, does damage.”

Karsha said with the help of various therapies, Levi was a healthy, happy boy whose movement had significantly improved.

“Levi is really kicking goals now,” she said. He can walk, stand in water and pull apart and piece together puzzles.”

Boston Children’s Hospital Dr Annapurna Poduri said the status quo had been to treat seizures like a symptom and try to find medications that alleviate them. But medications weren’t getting at the underlying causes of epilepsy, she said.

“We all feel a deep sense of responsibility to bring our genetic discovery successes to our patients,” Dr Poduri said. By bringing together experts from across the world in epilepsy and genomics, we demonstrated that if providing an underlying diagnosis to families and providers quickly was made a priority, we could better inform future treatment, evaluation, prognosis, and counseling for families of kids with infantile epilepsy."

SickKids Dr Gregory Costain said thanks to this international, multi-centre partnership, the team was able to demonstrate the feasibility and benefits of performing early rapid genome sequencing across four health-care systems.

“Our hope is that these findings will help us advocate for greater access to genome sequencing in clinical care and lay the groundwork for precision medicine interventions that could one day offer individualised treatment options for each patient and family,” he said.

Great Ormond Street Hospital’s Dr Amy McTague said the study had shown how this testing could be used to diagnose and inform treatment in many children.

“This has the potential to impact many families across the world and provide much needed information to clinical teams in charge of their care,” she said. We are incredibly grateful to every family that took part in this study, research like this is only possible because of them.”

Publication: Alissa M. D’Gama, Sarah Mulhern, MGenCouns, Beth R. Sheidley, Fadil Boodhoo, Sarah Buts, Natalie J. Chandler, Joanna Cobb, Meredith Curtis, Edward J. Higginbotham, Jonathon Holland, Tayyaba Khan, Julia Koh, Nicole S.Y. Liang, Lyndsey McRae, Sarah E. Nesbitt, Brandon T. Oby, Ben Paternoster, Alistair Patton, Graham Rose, Elizabeth Scotchman, Rozalia Valentine, Kimberly Wiltrout, Robin Z. Hayeems, Puneet Jain, Sebastian Lunke, Christian R. Marshall, Shira Rockowitz, Neil Sebire, Zornitza Stark, Susan M. White, Lyn S. Chitty, J. Helen Cross, Ingrid E. Scheffer, Vann Chau, Gregory Costain, Annapurna Poduri, Katherine B. Howell and Amy McTague. ‘Rapid genome sequencing in infantile epilepsy: an international, multicentre, prospective pilot cohort study,’ The Lancet Neurology. DOI: 10.1016/PIIS1474-4422(23)00246-6

*The content of this communication is the sole responsibility of the Murdoch Children’s and does not reflect the views of the NHMRC.

Available for interview:

Dr Katherine Howell, Murdoch Children’s, Team Leader, Neuroscience

Karsha Trowbridge whose son Levi, 3, has a rare genetic disorder that causes seizures